PROJECT SUMMARY Preterm birth involves deliveries before 37 weeks gestation. Approximately 15 million babies are born preterm every year in the world with a global prevalence approximating 10%. Prevalence of preterm birth in the US is approximately 13% and has increased in the US for decades. Risk factors of spontaneous preterm birth remain largely mysterious. An array of environmental exposures has been evaluated as potential risk factors for preterm birth including pesticides. Pesticide use in the US represents more than $2 billion/year in expenditures and involves the application of >100 million pounds of chemicals in the environment. Many of these chemical compounds are reproductive toxicants. However, large-scale studies have not been done to investigate whether gestational pesticide exposures influence preterm birth. This important public health hypothesis has been under studied likely owing to the limited availability of exposure data coupled with the lack of good epidemiologic data on preterm births. We have identified the necessary elements to remedy this lack of information. Here we propose the largest and most rigorous population-based epidemiologic study ever conducted that targets a breadth of pesticide compounds for their influence on preterm birth. We propose the following aims: 1) To determine whether exposures to specific pesticides during pregnancy are associated with >100,000 women spontaneously delivering infants/fetuses prematurely and 2) To determine whether exposures to biologically-functional groupings (e.g., endocrine disruptors or developmental toxicants) and physiochemical groupings (e.g., carbamates, halogenated hydrocarbons, and arsenicals) of pesticides during pregnancy are associated with >100,000 women spontaneously delivering infants/fetuses prematurely. Using existing data sources, we are proposing an unprecedented and efficient opportunity to close this knowledge gap. This population-scale study will be conducted in the California San Joaquin Valley - an area that is referred to as the food basket of the world and as the most productive agricultural region in the world. The San Joaquin Valley is an area with demonstrated extensive pesticide use and an area diverse in socioeconomic status and race/ethnic background. Our group has demonstrated capability to successfully carry out this project